4DGB

TRIMCyp cyclophilin domain from Macaca mulatta: HIV-2 CA cyclophilin-binding loop complex

Summary for 4DGB

• Entry DOI: 10.2210/pdb4dgb/pdb
• Related: 4DGA 4DGC 4DGD 4DGE
• Descriptor: TRIMCyp, capsid protein (3 entities in total)
• Functional Keywords: anti-viral protein, isomerase-viral protein complex, isomerase/viral protein
• Biological source: Macaca mulatta (rhesus macaque); More
• Cellular location: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential): P04590
• Total number of polymer chains: 2
• Total formula weight: 18567.12

Authors

Caines, M.E.C.,Bichel, K.,Price, A.J.,McEwan, W.A.,James, L.C. (deposition date: 2012-01-25, release date: 2012-02-08, Last modification date: 2023-09-13)

Primary citation

Caines, M.E.,Bichel, K.,Price, A.J.,McEwan, W.A.,Towers, G.J.,Willett, B.J.,Freund, S.M.,James, L.C.
Diverse HIV viruses are targeted by a conformationally dynamic antiviral.
Nat.Struct.Mol.Biol., 19:411-416, 2012

PubMed Abstract: Rhesus macaque TRIMCyp (RhTC) is a potent primate antiviral host protein that inhibits the replication of diverse HIV viruses. Here we show that it has acquired the ability to target multiple viruses by evolving an active site that interconverts between multiple conformations. Mutations that have relieved active site constraints allow RhTC to dynamically sample conformational space, including radically different conformers that target both HIV-1 and HIV-2 viruses. Introduction of a reversible constraint into RhTC allows specificity to be switched between a single conformation specific for HIV-1 and a dynamic ensemble that targets multiple viruses. These results show that conformational diversity can be used to expand the target diversity of innate immune receptors by supplementing their limited genetic variability with variability in protein structure.

PubMed: 22407016
DOI: 10.1038/nsmb.2253

Experimental method

X-RAY DIFFRACTION (1.702 Å)